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Biomedical subjects

J Stein

Publications and source records attributed to J Stein.

At least 397 records · Page 22Linked to original sources

A major human histone gene cluster on the long arm of chromosome 1.

A human histone gene cluster was assigned to chromosome 1 by Southern blot analysis of DNA's from a series of mouse-human somatic cell hybrids with 32P-labeled cloned human H4 and H3 histone DNA as probes. Localization of this histone gene cluster on the long arm of chromosome 1 was confirmed by in situ hybridization of this DNA probe to metaphase chromosomes.

Animals↗

A screening protocol for a prenatal population at risk for inherited hemoglobin disorders: results of its application to a group of Southeast Asians and blacks.

Several inherited hemoglobin disorders are present among certain racial subgroups of the United States population, particularly among blacks and Southeast Asians. Many of these disorders are unfamiliar to the obstetrician-gynecologist but may have important implications for care in pregnancy, including genetic counseling and prenatal diagnosis. A simple, effective screening tool was devised for detection of thalassemias and hemoglobinopathies in a prenatal clinic population. Use of the tool resulted in diagnosis of a hemoglobin disorder in 20% of a group of black patients; diagnoses included alpha-thalassemia trait, beta-thalassemia trait, hemoglobin C trait, hemoglobin S/C disease, hemoglobin S trait, sickle cell anemia, and hemoglobin Lepore. In a group of Southeast Asian patients, 39% had a hemoglobin disorder, including alpha-thalassemia trait, beta-thalassemia trait, hemoglobin E disease, and hemoglobin H disease. Implications for care are discussed.

Asia, Southeastern↗

Effects of oral mexiletine on left and right ventricular function.

Malignant ventricular arrhythmias often occur in patients with left ventricular (LV) dysfunction. Antiarrhythmic drugs may further impair LV function in these patients. Mexiletine, a lidocaine congener, is an effective antiarrhythmic drug, but when administered orally, its effect on LV and right ventricular (RV) function is unknown. To determine the hemodynamic effects of mexiletine, LV and RV ejection fraction (EF) were measured by radionuclide ventriculography in 10 patients with LV dysfunction (LVEF less than 50%). Symptom-limited exercise tests were also performed. Patients were studied before and during therapy with oral mexiletine. There was no significant change in LVEF (28% vs 27%) or RVEF (46% vs 41%). Also, heart rate at rest, exercise duration and peak heart rate during exercise were unchanged. Thus, in patients with LV dysfunction, oral mexiletine does not significantly affect LV or RV function.

Adult↗

Expression of histone genes in a G1-specific temperature-sensitive mutant of the cell cycle.

The expression of genes coding for the four core histones (H2A, H2B, H3, and H4) was studied in tsAF8 cells. These baby hamster kidney-derived cells are a temperature-sensitive (ts) mutant of the cell cycle that arrest in G1 at the restrictive temperature. When serum-deprived tsAF8 cells are stimulated with serum, they enter the S phase at the permissive temperature of 34 degrees C, but are blocked in G1 at the nonpermissive temperature of 39.6 degrees C. Northern blot analysis using cloned human histone DNA probes detected only very low levels of histone RNA either in quiescent tsAF8 cells or in cells serum stimulated at the nonpermissive temperature for 24 h. Cellular levels of histone RNA were markedly increased in cells serum stimulated at 34 degrees C for 24 h. Temperature shift-up experiments after serum stimulation of quiescent populations showed that the amount of histone RNA was related to the number of cells that entered the S phase. Those cells that synthesized histone RNA and entered the S phase were capable of dividing. This is the first demonstration in a mammalian G1-specific ts mutant that the expression of H2A, H2B, H3, and H4 histone genes depends on the entry of cells into the S phase of the cell cycle.

Animals↗

Clustering of human H1 and core histone genes.

An H1 histone gene was isolated from a 15-kilobase human DNA genomic sequence. The presence of H2A, H2B, H3, and H4 genes in this same 15-kilobase fragment indicates that mammalian core and H1 histone genes are clustered.

Animals↗

cis- and trans-Diamminedichloroplatinum(II)-mediated cross-linking of chromosomal non-histone proteins to DNA in HeLa cells.

The cross-linking of chromosomal non-histone proteins to DNA in isolated nuclei or intact HeLa cells exposed to different concentrations of cis- and trans-diamminedichloroplatinum(II) (cis- and trans-DDP) for various time intervals was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical methods. Both the cis- and the trans-DDP cross-linked significant numbers of chromosomal non-histone proteins to the DNA. The quantity and the types of the cross-linked proteins depended on the time of incubation as well as on the concentrations of the drugs. The immunochemical techniques revealed that both the 0.35 M sodium chloride insoluble and soluble chromosomal non-histone proteins were cross-linked to the DNA by both isomers. The action of cis- and trans-DDP was reversed and/or blocked by thiourea or 2-mercaptoethanol. Pretreatment of isolated nuclei or chromatin with iodoacetamide or N-ethylmaleimide did not prevent the DNA-protein cross-linking.

Chromosomal Proteins, Non-Histone↗

Inhibition of DNA replication coordinately reduces cellular levels of core and H1 histone mRNAs: requirement for protein synthesis.

Cellular levels of H1 and core histone mRNAs have been examined in exponentially growing HeLa S3 cells as a function of DNA synthesis inhibition under varying concentrations of three DNA synthesis inhibitors. Total cellular histone mRNAs were analyzed by Northern blot hybridization, and their relative abundance was shown to be stoichiometrically and temporally coupled to the rate of DNA synthesis. In the presence of cytosine arabinoside, hydroxyurea, or aphidicolin, a rapid, proportionate decrease of histone mRNA levels resulted in an apparent mRNA half-life of less than 10 min. Using inhibitors of transcription and translation, we show that transcription is not necessary for the coordinate decrease of histone mRNA levels that occurs when DNA synthesis is inhibited. When protein synthesis is inhibited by addition of cycloheximide, core and H1 histone mRNAs do not decrease in parallel with reduced rates of DNA synthesis but instead are stabilized and accumulate with time, thus uncoupling histone mRNA levels and DNA replication. These last observations suggest that protein synthesis, either of histones or of some unidentified regulatory molecules, is required for the stoichiometric turnover of H1 and core histone mRNAs coordinate with reduced rates of DNA synthesis.

Aphidicolin↗

Requirement of protein synthesis for the coupling of histone mRNA levels and DNA replication.

H1 and core histone mRNA levels have been examined in the presence of protein synthesis inhibitors with different mechanisms of action. Total HeLa cell RNAs were analyzed by Northern Blot hybridization using cloned human histone genes as probes. Inhibition of DNA replication resulted in a rapid decline in histone mRNA levels. However, in the presence of cycloheximide or puromycin, H1 and core mRNAs did not decrease in parallel with DNA synthesis, but were stabilized and accumulated. Inhibition of DNA synthesis with hydroxyurea after the inhibition of protein synthesis did not lead to a decline in histone mRNA levels. These results suggest that synthesis of a protein(s)--perhaps a histone protein(s)--is required for the coordination of DNA synthesis and histone mRNA levels.

Cloning, Molecular↗

Histone gene expression in human diploid fibroblasts: analysis of histone mRNA levels using cloned human histone genes.

The cellular abundance of H2A, H2B, H3 and H4 histone mRNA sequences was determined prior to and at various times after stimulation of non-dividing human diploid fibroblasts to proliferate. The representation of histone mRNAs was quantitated by electrophoretic fractionation of total cellular RNAs, diffusion transfer to nitrocellulose and hybridization with a series of cloned genomic human histone sequences. The levels of mRNAs for the four core histones were observed to be temporally and quantitatively coupled with both DNA replication and histone protein synthesis. Therefore, a contribution to the regulation of histone gene expression at a transcriptional level is suggested.

Cells, Cultured↗

Mesenteric venous thrombosis as sole complication of decompression sickness.

A 27-year-old male commercial diver developed massive mesenteric venous thrombosis following a dive. Symptoms at presentation included abdominal pain and diarrhea. A severe upper gastrointestinal bleed developed. Exploratory laparotomy demonstrated 130 cm of infarcted small bowel. The pathophysiologic events in decompression sickness predispose to vascular obstruction and venous infarction. This patient had a past history of possible thrombophlebitis and pulmonary embolism associated with diving but no identifiable coagulopathy.

Adult↗

Long-term mexiletine for ventricular arrhythmia.

Use of mexiletine was evaluated in 313 patients with ventricular tachyarrhythmias refractory to conventional antiarrhythmic drugs. Therapy with mexiletine was continued long term in 107 patients who responded to the drug and were free of side effects during a short-term evaluation in hospital. During an average follow-up of 22.8 months (0.1 to 70 months), 19 patients died (17.8%). Eleven patients had sudden death (3.6% per year), while six patients died of progressive congestive heart failure and two of noncardiac causes. Nonfatal ventricular arrhythmia recurred in 14 patients (4.9% per year). Overall, 25 patients had recurrent arrhythmia (incidence of 5.5% per year). Side effects occurred in 13 patients after an average of 5.1 months and were primarily gastrointestinal and neurologic. Sixty-one patients (57%) have continued on mexiletine therapy for an average of 32.2 months (1 to 70 months). Outcome during long-term therapy was not related to drug dose, blood level, or presenting arrhythmia. We conclude that if therapy with mexiletine is carefully evaluated and individualized, the drug is effective and well tolerated during long-term use.

Arrhythmias, Cardiac↗